title: Reno-protective role of flunarizine (mitochondrial permeability transition pore inactivator) against gentamicin induced nephrotoxicity in rats.
abstract: This study was aimed to evaluate the role of flunarizine on gentamicin (GEM) induced nephrotoxicity in rat. Administration of GEM (40 mg/kg, s.c. for 10 consecutive days) significantly increased blood urea nitrogen (BUN), N-acetyl β-d-glucosaminidase (NAG), thiobarbituric acid reactive substances (TBARS) and total calcium whereas, decreased body weight, fractional excretion of sodium (FrNa), creatinine clearance (CrCl), reduced glutathione (GSH), mitochondrial cytochrome c oxidase (Cyt-C oxidase) and ATP levels resulting in nephrotoxicity. Further, flunarizine (100, 200 and 300 µmol/kg, p.o.) was administered to evaluate its renoprotective effect against GEM induced nephrotoxicity and the results were compared with cylcosporin A (CsA, 50 µmol/kg, p.o.). Flunarizine resulted in the attenuation of renal dysfunction and oxidative marker changes in rats subjected to GEM induced nephrotoxicity in a dose dependent manner. Medium and higher doses of flunarizine produced significant renal protective effect which was comparable to cyclosporin A. The results of this study clearly revealed that flunarizine protected the kidney against the nephrotoxic effect of GEM via mitochondrial permeability transition pore (MPTP) inactivation potential.
authors.affiliation: Rayat Institute of Pharmacy, Ropar Campus, Nawanshahr District, Near Railmajra, Punjab, India. arunachalammu@gmail.com
authors.forename: Arunachalam
authors.initials: A
authors.lastname: Muthuraman
authors.forename: Sumeet Kumar
authors.initials: SK
authors.lastname: Singla
authors.forename: Ajay
authors.initials: A
authors.lastname: Rana
authors.forename: Atinderjeet
authors.initials: A
authors.lastname: Singh
authors.forename: Shailja
authors.initials: S
authors.lastname: Sood
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D016572:Cyclosporine / Q000627:therapeutic use; D005444:Flunarizine / Q000494:pharmacology / Q000627:therapeutic use*; D005839:Gentamicins / Q000633:toxicity*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D008297:Male; D033681:Mitochondrial Membrane Transport Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D000083162:Mitochondrial Permeability Transition Pore; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005839:Gentamicins; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D016572:Cyclosporine; D005444:Flunarizine